Abstract

We present a photoacoustic flow cytography with fast cross-sectional (B-scan) imaging to precisely identify specific cells in vivo. The B-scan imaging speed of the system is up to 200 frame/s with a lateral resolution of 1.5 μm, which allows to dynamically image the flowing cells within the microvascular. The shape, size and photoacoustic intensity of the target cells are extracted from streaming images and integrated into a standard pattern to distinguish cell types. Circulating red blood cells and melanoma cells in blood vessels are simultaneously identified on melanoma-bearing mouse model. The results demonstrate that in vivo photoacoustic flow cytography can provide cells characteristics analysis and cell type’s visual identification, which will be applied for noninvasively monitoring circulating tumor cells (CTCs) and analyzing hematologic diseases.

© 2015 Optical Society of America

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    [Crossref] [PubMed]
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    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  29. V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal image flow cytometry in vivo,” Opt. Lett. 30(6), 628–630 (2005).
    [Crossref] [PubMed]
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2015 (1)

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

2014 (3)

C. M. Svensson, S. Krusekopf, J. Lücke, and M. Thilo Figge, “Automated detection of circulating tumor cells with naive bayesian classifiers,” Cytometry A 85(6), 501–511 (2014).
[Crossref] [PubMed]

D. A. Nedosekin, V. V. Verkhusha, A. V. Melerzanov, V. P. Zharov, and E. I. Galanzha, “In vivo photoswitchable flow cytometry for direct tracking of single circulating tumor cells,” Chem. Biol. 21(6), 792–801 (2014).
[Crossref] [PubMed]

R. R. Liu, C. Wang, C. Hu, X. D. Wang, and X. B. Wei, “In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry,” Proc. SPIE 8944, 89440Q (2014).
[Crossref]

2013 (6)

2012 (5)

L. Zeng, G. Liu, D. Yang, and X. Ji, “3D-visual laser-diode-based photoacoustic imaging,” Opt. Express 20(2), 1237–1246 (2012).
[Crossref] [PubMed]

Z. Chen, S. Yang, and D. Xing, “In vivo detection of hemoglobin oxygen saturation and carboxyhemoglobin saturation with multiwavelength photoacoustic microscopy,” Opt. Lett. 37(16), 3414–3416 (2012).
[Crossref] [PubMed]

E. I. Galanzha and V. P. Zharov, “Photoacoustic flow cytometry,” Methods 57(3), 280–296 (2012).
[Crossref] [PubMed]

T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, “Separation of blood cells using hydrodynamic lift,” Appl. Phys. Lett. 100(18), 183701 (2012).
[Crossref]

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

2011 (4)

2009 (3)

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3(9), 503–509 (2009).
[Crossref] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[Crossref] [PubMed]

2007 (1)

W. He, H. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[Crossref] [PubMed]

2006 (2)

V. P. Zharov, E. I. Galanzha, Y. Menyaev, and V. V. Tuchin, “In vivo high-speed imaging of individual cells in fast blood flow,” J. Biomed. Opt. 11(5), 054034 (2006).
[Crossref] [PubMed]

L. D. F. Costa and E. Bollt, “Fast and accurate nonlinear spectral method for image recognition and registration,” Appl. Phys. Lett. 89(17), 174102 (2006).
[Crossref]

2005 (1)

2004 (1)

2003 (1)

F. Kubota, “Analysis of red cell and platelet morphology using an imaging-combined flow cytometer,” Clin. Lab. Haematol. 25(2), 71–76 (2003).
[Crossref] [PubMed]

1992 (1)

J. D. Losek, T. R. Hellmich, and G. M. Hoffman, “Diagnostic value of anemia, red blood cell morphology, and reticulocyte count for sickle cell disease,” Ann. Emerg. Med. 21(8), 915–918 (1992).
[Crossref] [PubMed]

1983 (1)

M. P. Westerman and J. W. Bacus, “Red blood cell morphology in sickle cell anemia as determined by image processing analysis: the relationship to painful crises,” Am. J. Clin. Pathol. 79(6), 667–672 (1983).
[PubMed]

Albert, M. L.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Bacus, J. W.

M. P. Westerman and J. W. Bacus, “Red blood cell morphology in sickle cell anemia as determined by image processing analysis: the relationship to painful crises,” Am. J. Clin. Pathol. 79(6), 667–672 (1983).
[PubMed]

Beitz, B.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Bertrand, F. E.

Bollt, E.

L. D. F. Costa and E. Bollt, “Fast and accurate nonlinear spectral method for image recognition and registration,” Appl. Phys. Lett. 89(17), 174102 (2006).
[Crossref]

Braunmüller, S.

T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, “Separation of blood cells using hydrodynamic lift,” Appl. Phys. Lett. 100(18), 183701 (2012).
[Crossref]

Brock, R. S.

Chalmond, B.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Chen, C.

Chen, X.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Chen, Z.

Cheng, J. X.

W. He, H. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[Crossref] [PubMed]

Costa, L. D. F.

L. D. F. Costa and E. Bollt, “Fast and accurate nonlinear spectral method for image recognition and registration,” Appl. Phys. Lett. 89(17), 174102 (2006).
[Crossref]

Ding, Y.

Dong, K.

Duffy, D.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Eggart, B.

T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, “Separation of blood cells using hydrodynamic lift,” Appl. Phys. Lett. 100(18), 183701 (2012).
[Crossref]

Fan, Z.

Farwell, M. A.

Feng, Y.

Franke, T.

T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, “Separation of blood cells using hydrodynamic lift,” Appl. Phys. Lett. 100(18), 183701 (2012).
[Crossref]

Galanzha, E. I.

D. A. Nedosekin, V. V. Verkhusha, A. V. Melerzanov, V. P. Zharov, and E. I. Galanzha, “In vivo photoswitchable flow cytometry for direct tracking of single circulating tumor cells,” Chem. Biol. 21(6), 792–801 (2014).
[Crossref] [PubMed]

Y. A. Menyaev, D. A. Nedosekin, M. Sarimollaoglu, M. A. Juratli, E. I. Galanzha, V. V. Tuchin, and V. P. Zharov, “Optical clearing in photoacoustic flow cytometry,” Biomed. Opt. Express 4(12), 3030–3041 (2013).
[Crossref] [PubMed]

E. I. Galanzha and V. P. Zharov, “Photoacoustic flow cytometry,” Methods 57(3), 280–296 (2012).
[Crossref] [PubMed]

E. I. Galanzha and V. P. Zharov, “In vivo photoacoustic and photothermal cytometry for monitoring multiple blood rheology parameters,” Cytometry A 79(10), 746–757 (2011).
[Crossref] [PubMed]

M. Sarimollaoglu, D. A. Nedosekin, Y. Simanovsky, E. I. Galanzha, and V. P. Zharov, “In vivo photoacoustic time-of-flight velocity measurement of single cells and nanoparticles,” Opt. Lett. 36(20), 4086–4088 (2011).
[Crossref] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[Crossref] [PubMed]

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

V. P. Zharov, E. I. Galanzha, Y. Menyaev, and V. V. Tuchin, “In vivo high-speed imaging of individual cells in fast blood flow,” J. Biomed. Opt. 11(5), 054034 (2006).
[Crossref] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal image flow cytometry in vivo,” Opt. Lett. 30(6), 628–630 (2005).
[Crossref] [PubMed]

Geislinger, T. M.

T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, “Separation of blood cells using hydrodynamic lift,” Appl. Phys. Lett. 100(18), 183701 (2012).
[Crossref]

Georgakoudi, I.

Greve, J.

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

Hartmann, L. C.

W. He, H. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[Crossref] [PubMed]

Hasan, M.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

He, W.

W. He, H. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[Crossref] [PubMed]

Hellmich, T. R.

J. D. Losek, T. R. Hellmich, and G. M. Hoffman, “Diagnostic value of anemia, red blood cell morphology, and reticulocyte count for sickle cell disease,” Ann. Emerg. Med. 21(8), 915–918 (1992).
[Crossref] [PubMed]

Hoffman, G. M.

J. D. Losek, T. R. Hellmich, and G. M. Hoffman, “Diagnostic value of anemia, red blood cell morphology, and reticulocyte count for sickle cell disease,” Ann. Emerg. Med. 21(8), 915–918 (1992).
[Crossref] [PubMed]

Hu, C.

R. R. Liu, C. Wang, C. Hu, X. D. Wang, and X. B. Wei, “In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry,” Proc. SPIE 8944, 89440Q (2014).
[Crossref]

Hu, X. H.

Jacobs, K. M.

Jalali, B.

Ji, X.

Juratli, M. A.

Kelly, T.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

Kim, J. W.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

Krusekopf, S.

C. M. Svensson, S. Krusekopf, J. Lücke, and M. Thilo Figge, “Automated detection of circulating tumor cells with naive bayesian classifiers,” Cytometry A 85(6), 501–511 (2014).
[Crossref] [PubMed]

Kubota, F.

F. Kubota, “Analysis of red cell and platelet morphology using an imaging-combined flow cytometer,” Clin. Lab. Haematol. 25(2), 71–76 (2003).
[Crossref] [PubMed]

Libri, V.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Ligthart, S. T.

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

Lin, C. P.

Liu, G.

Liu, R. R.

R. R. Liu, C. Wang, C. Hu, X. D. Wang, and X. B. Wei, “In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry,” Proc. SPIE 8944, 89440Q (2014).
[Crossref]

Losek, J. D.

J. D. Losek, T. R. Hellmich, and G. M. Hoffman, “Diagnostic value of anemia, red blood cell morphology, and reticulocyte count for sickle cell disease,” Ann. Emerg. Med. 21(8), 915–918 (1992).
[Crossref] [PubMed]

Low, P. S.

W. He, H. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[Crossref] [PubMed]

Lu, J. Q.

Lücke, J.

C. M. Svensson, S. Krusekopf, J. Lücke, and M. Thilo Figge, “Automated detection of circulating tumor cells with naive bayesian classifiers,” Cytometry A 85(6), 501–511 (2014).
[Crossref] [PubMed]

Luo, Q.

Mahjoubfar, A.

Maslov, K.

L. Wang, K. Maslov, and L. V. Wang, “Single-cell label-free photoacoustic flowoxigraphy in vivo,” Proc. Natl. Acad. Sci. U.S.A. 110(15), 5759–5764 (2013).
[Crossref] [PubMed]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, “Fast voice-coil scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 36(2), 139–141 (2011).
[Crossref] [PubMed]

Maslov, K. I.

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111(20), 204301 (2013).
[Crossref] [PubMed]

Melerzanov, A. V.

D. A. Nedosekin, V. V. Verkhusha, A. V. Melerzanov, V. P. Zharov, and E. I. Galanzha, “In vivo photoswitchable flow cytometry for direct tracking of single circulating tumor cells,” Chem. Biol. 21(6), 792–801 (2014).
[Crossref] [PubMed]

Meng, J.

J. Meng and L. Song, “Biomedical photoacoustics in China,” Photoacoustics 1(2), 43–48 (2013).
[Crossref] [PubMed]

Menyaev, Y.

V. P. Zharov, E. I. Galanzha, Y. Menyaev, and V. V. Tuchin, “In vivo high-speed imaging of individual cells in fast blood flow,” J. Biomed. Opt. 11(5), 054034 (2006).
[Crossref] [PubMed]

Menyaev, Y. A.

Nedosekin, D. A.

Niazi, K. R.

Novak, J.

Patin, É.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Prossin, A.

Quintana-Murci, L.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Rabizadeh, S.

Rao, B.

Rogge, L.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Rouilly, V.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Sarimollaoglu, M.

Schmid, L.

T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, “Separation of blood cells using hydrodynamic lift,” Appl. Phys. Lett. 100(18), 183701 (2012).
[Crossref]

Scholtens, T. M.

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

Schreuder, F.

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

Schwikowski, B.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Shashkov, E. V.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[Crossref] [PubMed]

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

Shi, R.

Simanovsky, Y.

Song, L.

J. Meng and L. Song, “Biomedical photoacoustics in China,” Photoacoustics 1(2), 43–48 (2013).
[Crossref] [PubMed]

Spring, P. M.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[Crossref] [PubMed]

Suen, J. Y.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[Crossref] [PubMed]

Svensson, C. M.

C. M. Svensson, S. Krusekopf, J. Lücke, and M. Thilo Figge, “Automated detection of circulating tumor cells with naive bayesian classifiers,” Cytometry A 85(6), 501–511 (2014).
[Crossref] [PubMed]

Swennenhuis, J. F.

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

Terstappen, L. W.

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

Thilo Figge, M.

C. M. Svensson, S. Krusekopf, J. Lücke, and M. Thilo Figge, “Automated detection of circulating tumor cells with naive bayesian classifiers,” Cytometry A 85(6), 501–511 (2014).
[Crossref] [PubMed]

Tuchin, V. V.

Urrutia, A.

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Verkhusha, V. V.

D. A. Nedosekin, V. V. Verkhusha, A. V. Melerzanov, V. P. Zharov, and E. I. Galanzha, “In vivo photoswitchable flow cytometry for direct tracking of single circulating tumor cells,” Chem. Biol. 21(6), 792–801 (2014).
[Crossref] [PubMed]

Wang, C.

R. R. Liu, C. Wang, C. Hu, X. D. Wang, and X. B. Wei, “In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry,” Proc. SPIE 8944, 89440Q (2014).
[Crossref]

Wang, H.

W. He, H. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[Crossref] [PubMed]

Wang, J.

Wang, L.

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111(20), 204301 (2013).
[Crossref] [PubMed]

L. Wang, K. Maslov, and L. V. Wang, “Single-cell label-free photoacoustic flowoxigraphy in vivo,” Proc. Natl. Acad. Sci. U.S.A. 110(15), 5759–5764 (2013).
[Crossref] [PubMed]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, “Fast voice-coil scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 36(2), 139–141 (2011).
[Crossref] [PubMed]

Wang, L. V.

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111(20), 204301 (2013).
[Crossref] [PubMed]

L. Wang, K. Maslov, and L. V. Wang, “Single-cell label-free photoacoustic flowoxigraphy in vivo,” Proc. Natl. Acad. Sci. U.S.A. 110(15), 5759–5764 (2013).
[Crossref] [PubMed]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, “Fast voice-coil scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 36(2), 139–141 (2011).
[Crossref] [PubMed]

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3(9), 503–509 (2009).
[Crossref] [PubMed]

Wang, X. D.

R. R. Liu, C. Wang, C. Hu, X. D. Wang, and X. B. Wei, “In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry,” Proc. SPIE 8944, 89440Q (2014).
[Crossref]

Wei, D.

Wei, X.

Wei, X. B.

R. R. Liu, C. Wang, C. Hu, X. D. Wang, and X. B. Wei, “In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry,” Proc. SPIE 8944, 89440Q (2014).
[Crossref]

Westerman, M. P.

M. P. Westerman and J. W. Bacus, “Red blood cell morphology in sickle cell anemia as determined by image processing analysis: the relationship to painful crises,” Am. J. Clin. Pathol. 79(6), 667–672 (1983).
[PubMed]

Xia, J.

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111(20), 204301 (2013).
[Crossref] [PubMed]

Xing, D.

Yang, D.

Yang, L.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

Yang, L. V.

Yang, S.

Yao, J.

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111(20), 204301 (2013).
[Crossref] [PubMed]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, “Fast voice-coil scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 36(2), 139–141 (2011).
[Crossref] [PubMed]

Zeng, L.

Zharov, V. P.

D. A. Nedosekin, V. V. Verkhusha, A. V. Melerzanov, V. P. Zharov, and E. I. Galanzha, “In vivo photoswitchable flow cytometry for direct tracking of single circulating tumor cells,” Chem. Biol. 21(6), 792–801 (2014).
[Crossref] [PubMed]

Y. A. Menyaev, D. A. Nedosekin, M. Sarimollaoglu, M. A. Juratli, E. I. Galanzha, V. V. Tuchin, and V. P. Zharov, “Optical clearing in photoacoustic flow cytometry,” Biomed. Opt. Express 4(12), 3030–3041 (2013).
[Crossref] [PubMed]

E. I. Galanzha and V. P. Zharov, “Photoacoustic flow cytometry,” Methods 57(3), 280–296 (2012).
[Crossref] [PubMed]

E. I. Galanzha and V. P. Zharov, “In vivo photoacoustic and photothermal cytometry for monitoring multiple blood rheology parameters,” Cytometry A 79(10), 746–757 (2011).
[Crossref] [PubMed]

M. Sarimollaoglu, D. A. Nedosekin, Y. Simanovsky, E. I. Galanzha, and V. P. Zharov, “In vivo photoacoustic time-of-flight velocity measurement of single cells and nanoparticles,” Opt. Lett. 36(20), 4086–4088 (2011).
[Crossref] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[Crossref] [PubMed]

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

V. P. Zharov, E. I. Galanzha, Y. Menyaev, and V. V. Tuchin, “In vivo high-speed imaging of individual cells in fast blood flow,” J. Biomed. Opt. 11(5), 054034 (2006).
[Crossref] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal image flow cytometry in vivo,” Opt. Lett. 30(6), 628–630 (2005).
[Crossref] [PubMed]

Zhu, D.

Am. J. Clin. Pathol. (1)

M. P. Westerman and J. W. Bacus, “Red blood cell morphology in sickle cell anemia as determined by image processing analysis: the relationship to painful crises,” Am. J. Clin. Pathol. 79(6), 667–672 (1983).
[PubMed]

Ann. Emerg. Med. (1)

J. D. Losek, T. R. Hellmich, and G. M. Hoffman, “Diagnostic value of anemia, red blood cell morphology, and reticulocyte count for sickle cell disease,” Ann. Emerg. Med. 21(8), 915–918 (1992).
[Crossref] [PubMed]

Appl. Phys. Lett. (2)

T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, “Separation of blood cells using hydrodynamic lift,” Appl. Phys. Lett. 100(18), 183701 (2012).
[Crossref]

L. D. F. Costa and E. Bollt, “Fast and accurate nonlinear spectral method for image recognition and registration,” Appl. Phys. Lett. 89(17), 174102 (2006).
[Crossref]

Biomed. Opt. Express (4)

Cancer Res. (1)

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[Crossref] [PubMed]

Chem. Biol. (1)

D. A. Nedosekin, V. V. Verkhusha, A. V. Melerzanov, V. P. Zharov, and E. I. Galanzha, “In vivo photoswitchable flow cytometry for direct tracking of single circulating tumor cells,” Chem. Biol. 21(6), 792–801 (2014).
[Crossref] [PubMed]

Clin. Immunol. (1)

X. Chen, M. Hasan, V. Libri, A. Urrutia, B. Beitz, V. Rouilly, D. Duffy, É. Patin, B. Chalmond, L. Rogge, L. Quintana-Murci, M. L. Albert, B. Schwikowski, and Milieu Intérieur Consortium, “Automated flow cytometric analysis across large numbers of samples and cell types,” Clin. Immunol. 157(2), 249–260 (2015).
[Crossref] [PubMed]

Clin. Lab. Haematol. (1)

F. Kubota, “Analysis of red cell and platelet morphology using an imaging-combined flow cytometer,” Clin. Lab. Haematol. 25(2), 71–76 (2003).
[Crossref] [PubMed]

Cytometry A (3)

C. M. Svensson, S. Krusekopf, J. Lücke, and M. Thilo Figge, “Automated detection of circulating tumor cells with naive bayesian classifiers,” Cytometry A 85(6), 501–511 (2014).
[Crossref] [PubMed]

T. M. Scholtens, F. Schreuder, S. T. Ligthart, J. F. Swennenhuis, J. Greve, and L. W. Terstappen, “Automated identification of circulating tumor cells by image cytometry,” Cytometry A 81(2), 138–148 (2012).
[Crossref] [PubMed]

E. I. Galanzha and V. P. Zharov, “In vivo photoacoustic and photothermal cytometry for monitoring multiple blood rheology parameters,” Cytometry A 79(10), 746–757 (2011).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

V. P. Zharov, E. I. Galanzha, Y. Menyaev, and V. V. Tuchin, “In vivo high-speed imaging of individual cells in fast blood flow,” J. Biomed. Opt. 11(5), 054034 (2006).
[Crossref] [PubMed]

Methods (1)

E. I. Galanzha and V. P. Zharov, “Photoacoustic flow cytometry,” Methods 57(3), 280–296 (2012).
[Crossref] [PubMed]

Nat. Nanotechnol. (1)

E. I. Galanzha, E. V. Shashkov, T. Kelly, J. W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[Crossref] [PubMed]

Nat. Photonics (1)

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3(9), 503–509 (2009).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (5)

Photoacoustics (1)

J. Meng and L. Song, “Biomedical photoacoustics in China,” Photoacoustics 1(2), 43–48 (2013).
[Crossref] [PubMed]

Phys. Rev. Lett. (1)

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111(20), 204301 (2013).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

L. Wang, K. Maslov, and L. V. Wang, “Single-cell label-free photoacoustic flowoxigraphy in vivo,” Proc. Natl. Acad. Sci. U.S.A. 110(15), 5759–5764 (2013).
[Crossref] [PubMed]

W. He, H. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[Crossref] [PubMed]

Proc. SPIE (1)

R. R. Liu, C. Wang, C. Hu, X. D. Wang, and X. B. Wei, “In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry,” Proc. SPIE 8944, 89440Q (2014).
[Crossref]

Other (1)

L. D. F. Costa and R. M. Cesar, Jr., “Shape classification and analysis theory and practice,” (Crc Press Taylor & Francis Group 2009).

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Figures (5)

Fig. 1
Fig. 1 (a) Schematic of photoacoustic flow cytography. LWDPO, long working distance plan objective (20 × , NA = 0.55). DAQ, data acquisition. CCD, charge coupled device. (b) The PA image of a sharp edge. (c) Estimation of lateral resolution. ESF, edge spread function. LSF, line spread function.
Fig. 2
Fig. 2 (a) Absorption spectra of solutions with the mixture of WBCs and PLT, RBCs, B16F10 cells, plasma and PBS, respectively. (b) The corresponding PA signal intensities at 532 nm.
Fig. 3
Fig. 3 Morphology comparison. (a), (b) and (c) PA images of RBCs, adherent melanoma B16F10 cells, and suspended B16F10 cells in RBCs. The scanning interval was 1 μm. (d), (e) and (f) The corresponding optical microscope images.
Fig. 4
Fig. 4 Characteristic extraction and identification. (a) Processes of obtaining cell diameters after edge detection, filling holes and extraction. Dl and Ds were the long and short diameters. (b) The maximum PA signal intensity extracted from a B16F10 cell image. The bar shown in figures represents 3 μm. (c) Scatter plot of the long versus short diameters. (d) Scatter plot of the long diameter and PA intensity. (e) Scatter plot of the Γ parameters of cells. The hollow circles are RBCs and the filled circles are B16F10 cells.
Fig. 5
Fig. 5 In vivo recognition of RBCs and melanoma CTCs. (a) PA image of a capillary at the edge of a mouse ear. (b) B-scan x-t image of cells in vessels located in (a). (c) Melanoma tumor growth in mouse dorsum. (d) The superficial microvasculature PA image in a mouse ear. (e) B-scan x-t image of cells in a selected vessel labeled x3 in (d). The diameters of selected vessels were 10 μm, 18 μm and 15 μm respectively. The white dotted lines represented walls of vessels. And the recognized melanoma CTCs and RBCs were labeled with yellow and white squares respectively. (f) The number of melanoma CTCs recorded in one minute as a function of weeks after tumor inoculation.

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